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  1. Home
  2. Books
  3. Principles and Practice of Fertility Preservation
  • Cited by 7
Publisher:
Cambridge University Press
Online publication date:
February 2011
Print publication year:
2011
Online ISBN:
9780511921896
DOI:
https://doi.org/10.1017/CBO9780511921896
Subjects:
Oncology, Obstetrics and Gynecology, Reproductive Medicine, Medicine
Information

Book description

The specialty of fertility preservation offers patients with cancer, who are rendered infertile by chemo- and radiotherapy, the opportunity to realize their reproductive potential. This gold-standard publication defines the specialty. The full range of techniques and scientific concepts is covered in detail, and the author team includes many of the world's leading experts in the field. The book opens with introductions to fertility preservation in both cancer and non-cancer patients, followed by cancer biology, epidemiology and treatment, and reproductive biology and cryobiology. Subsequent sections cover fertility preservation strategies in males and females, including medical/surgical procedures, ART, cryopreservation and transplantation of both ovarian tissue and the whole ovary, and in-vitro follicle growth and maturation. Concluding chapters address future technologies, as well as ethical, legal and religious issues. Richly illustrated throughout, this is a key resource for all clinicians specializing in reproductive medicine, gynecology, oncology, hematology, endocrinology and infertility.

Reviews

'One of the outstanding features of this book is the merging of oncology and reproduction so that people in both fields will benefit from reading it … appropriate for a wide audience.'

Source: Doody's Notes

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Contents

Page 2 of 3

Contents
  • Chapter 17 - Assisted reproductive techniques and donor sperm in cancer patients
    pp 225-238
  • View abstract

    Summary

    Childhood tumors are classified into 12 major diagnostic groups: leukemias, lymphomas, central nervous system (CNS) tumors, sympathetic nervous system tumors, retinoblastomas, renal tumors, liver tumors, bone tumors, soft tissue sarcomas, germ cell tumors, epithelial tumors and other and unspecified malignant cancers. Epidemiological studies have shown an association between exposure to medical radiation during pregnancy and risk of childhood cancer in offspring. The effects of maternal lifestyle during pregnancy on embryonic and fetal development are well known effects on the subsequent risk of cancer. Several features of maternal lifestyle during pregnancy have been studied regarding their association with childhood cancer, including diet, breastfeeding, smoking and alcohol consumption and the use of cosmetics. Parental illicit drugs use has been associated with several types of childhood cancer. Lymphoma, melanoma and testicular, cervical and thyroid cancers account for the vast majority of cancers in adolescents and young adults.
  • Chapter 18 - Use of GnRH agonists for prevention of chemotherapy-induced gonadotoxicity
    pp 239-249
  • View abstract

    Summary

    This chapter focuses specifically on how apoptosis affects sperm quality and function, and the implications of this process for both embryonic development and the health and well-being of the offspring. DNA damage in human spermatozoa has been correlated with poor fertilization and impaired embryonic development to the blastocyst stage as well as with the incidence of subsequent miscarriage. Human infertility is a complex multifactorial condition that is strongly impacted by genetic factors that assisted reproductive technology (ART) will ensure are passed onto the progeny. Spermiogenesis is a key event in the etiology of DNA damage in the male germ line. DNA damage in human spermatozoa appears to have its origins in the testes and is associated with oxidative stress. Spermatozoa possess several variants of the prolactin receptor and respond to the presence of this hormone with the stimulation of PI3 kinase/Akt phosphorylation and the prolongation of sperm survival.
  • Chapter 20 - Fertility-saving surgery for cervical cancer
    pp 257-265
  • View abstract

    Summary

    The follicle has a fundamental reproductive role in the ovary. Follicle growth takes 85 days in humans and most follicles become artistic at some stage with the oocyte continuing to play a critical role in follicular control and the regulation of oogenesis, ovulation rate and fecundity. The first primordial follicle in human foetuses is formed at 15-22 week gestation, at which point oocytes are enclosed by a single layer of pre-granulosa cells. Upon activation of primordial follicles, progression from the primary to secondary stage of follicular development requires further oocyte expansion, granulosa cell (GC) proliferation and investment of a luteinizing hormone (LH)-responsive theca cell layer. The pre-antral follicle continues its development and becomes increasingly follicle stimulating hormone (FSH) responsive. Follicular antrum formation and antral expansion are absolutely dependent on FSH. Luteinizing hormone appears to play a major role in mediating the final phase of follicular development.
  • Chapter 21 - Results of conservative management of ovarian malignant tumors
    pp 266-278
  • View abstract

    Summary

    Understanding the basics of cryobiology to develop improved cryopreservation procedures has been a major challenge to scientists all over the world. During a typical cryopreservation process ice tends to form at different rates. Intracellular ice formation is generally thought to be lethal as it causes injury to cellular membranes and intracellular structures. Conventional slow freezing protocols involve pretreatment of cells with cryoprotective agents (CPAs) in order to remove some water from the cells and to minimize some other harmful effects of freezing. The rate at which permeable CPA diffuses into the cells varies between the cryoprotectants and is also temperature and concentration dependant. Vitrification has become an increasingly accepted method for preserving embryos, oocytes and, recently, even sperm. An ideal vitrification method produces no ice formation and may therefore be an equilibrium method. The benefits of sperm cryopreservation are numerous in human reproductive medicine.
  • Chapter 22 - Embryo cryopreservation as a fertility preservation strategy
    pp 279-282
  • View abstract

    Summary

    In the field of assisted reproductive technology, vitrification is becoming an increasingly popular method of cryopreserving cells, tissues and even entire organs. The possibility that water might be vitrified was first proposed by Brayley in the mid 1800s, but the idea of cryopreservation by vitrification was apparently not introduced until Stiles observed, that protoplasm is likely, at very high cooling rates, to form "a finely crystalline or even amorphous mass" that "in thawing, might be expected to give again the original system without change". Vitrification does not inherently rely upon very high rates of cooling because ice nucleation and growth rates go down as solute concentration goes up. Vitrification can be seen as the means by which an aqueous solution remains within the bounds of thermodynamic law. The negative effects of vitrification solutions (VSs) can arise, not only from true biochemical toxicity but also from osmotic effects.
  • Chapter 23 - Oocyte cryopreservation
    pp 283-292
  • Slow freezing
  • View abstract

    Summary

    This chapter discusses the current knowledge of hormonal suppression as a means to preserve or restore fertility in males. The seminiferous tubules contain the germ cells, which consist of stem and differentiating spermatogonia, spermatocytes, spermatids and sperm and the sertoli cells, which support and regulate germ cell differentiation. The eventual recovery of sperm production depends on the survival of the spermatogonial stem cells and their ability to differentiate after exposure to cytotoxic agents. Several studies support the conclusion that gonadotropin suppression does not protect spermatogenesis in mice from damage. Seven clinical trials have been performed in attempts to demonstrate protection of spermatogenesis in humans by hormone suppression treatment before and during cytotoxic therapy, but six indicated no protection. One contribution to the difference in the stimulation of recovery by hormone suppression after cytotoxic treatment may be the interspecies differences in the block in differentiation of spermatogonia.
  • Chapter 25 - Cryopreservation and transplantation of isolated follicles
    pp 305-309
  • View abstract

    Summary

    Cryopreservation of male and female gametes has been long established, and nowadays low-temperature storage of human spermatozoa is a routine technique in assisted reproduction. The vitrification method uses no specially developed cooling program; it does not need to apply permeable cryoprotectants; it is much faster, simpler and cheaper; and it can also provide a high recovery of motile spermatozoa after warming as effective protection of spermatozoa against cryodamage. Higher concentrations of cryoprotectants are needed for extracellular than for intracellular vitrification. The success of Luyet's vitrification technique was supported by Shaffner applying the technique to frog spermatozoa after vitrification of fowl sperm. The advantage of programmable or non-programmable conventional slow freezing is the ability to simultaneously preserve a relatively large volume of diluted ejaculate or prepared spermatozoa. Long-term storage of frozen cells and tissues remains elusive in both theoretical and routine cryobiology, and future investigation applying nanotechnology is needed.
  • Chapter 26 - ART and oocyte donation in cancer survivors
    pp 310-327
  • View abstract

    Summary

    Over the last several decades, survival rates for childhood cancer have steadily increased. Spermatogonial stem cells are responsible for the continual production of spermatozoa throughout adult life. Autotransplantation is considered more acceptable than allotransplantation or xenotransplantation, although both of the latter have been used successfully in mouse models. Spermatogenesis in vitro from biopsied germ cells is considered to be an excellent alternative for pre-pubertal boys with malignancies, particularly of hematopoietic origin, who carry a risk of relapse after transplantation. Despite significant advances in spermatogonial cell biology and subsequent fertility management, malignant contamination remains one of the main concerns surrounding autologous transplantation. The potential for transferring tumor cells within cryopreserved and subsequently cultured and/or expanded testicular tissue back into the patient is of paramount concern. Children most at risk of transmitting cancer cells include those with a haematological malignancy such as acute leukemia.
  • Chapter 27 - General overview of ovarian cryobanking
    pp 328-341
  • View abstract

    Summary

    Loss of fertility in adult life is a major psychologically traumatic consequence of cancer treatment. Improving therapeutic regimens using less gonadotoxic protocols could enable spontaneous recovery of spermatogenesis, but their use is not always possible without compromising patient survival. Cryopreservation of testicular tissue pieces may be considered as an alternative method capable of maintaining cell-to-cell contacts between Sertoli and germinal stem cells, and therefore preserving the stem cell niche necessary for their survival and subsequent maturation. In humans, preclinical in vitro studies using cadaver or surgically removed testes have demonstrated the feasibility of transplanting germ cell suspensions into testes. The first convincing demonstration of human testis transplantation was reported in 1978. The most important, life-threatening concern of spermatogonial transplantation is the risk of reintroducing malignant cells. Providing young people undergoing gonadotoxic treatment with adequate fertility preservation strategies is a challenging area of reproductive medicine.
  • Chapter 28 - Ovarian tissue cryopreservation
    pp 342-356
  • View abstract

    Summary

    This chapter focuses on patients with testicular cancer and lymphoma that generally affects younger patients in the reproductive window with an excellent overall survival. The chance of recovery of spermatogenesis depends on the chemotherapeutic regimen as well as the baseline function of the patient. The existence of a previously cryopreserved sperm greatly simplifies the algorithm for the post chemotherapeutic azoospermic man and, essentially, the couple can go directly to in vitro fertilization (IVF). Azoospermia after chemotherapy can be due to the patient's chemotherapeutic regimen, the use of radiation, the extent of surgery, the disease itself, the baseline function of the patient or any combination of the aforementioned factors. Additional counseling is recommended for those patients who choose the assistance of third-party reproduction. Gamete donation has made it possible for participants to cross generational lines and has raised many complicated ethical issues.
  • Chapter 29 - Ovarian tissue transplantation
    pp 357-366
  • View abstract

    Summary

    The use of gonadotropin-releasing hormone agonists (GnRHa) for prevention of chemotherapy-induced gonadotoxicity remains controversial. With the initial dose of GnRHa, the pituitary gland releases endogenous gonadotropins. This initial follicle stimulating hormone (FSH) release stimulates the ovary. After continued GnRHa exposure, further FSH release is prevented. Gonadotropin-releasing hormone analogues can be administered in many formulations with different durations of action. The most common side effects of GnRH analogues are related to the subsequent estrogen deprivation. Vasomotor symptoms, hot flushes, night sweats, vaginal dryness and headaches can occur. Cotherapy of a GnRHa during chemotherapy has been under investigation since the mid 1990s. If prolonged GnRHa administration decreases ovarian blood flow, then less chemotherapy may reach the ovary. Direct effects of GnRHa or FSH on ovarian tissue may influence ovarian response to chemotherapy. For GnRHa to be of benefit to fertility preservation, they would likely need to spare both oocyte quantity and quality.
  • Chapter 31 - Ovarian transplantation
    pp 377-388
  • Whole ovary transplantation
  • View abstract

    Summary

    The relocation of ovaries for their protection in women diagnosed with cancer in the pelvis was mentioned as early as 1958 by McCall et al. At that time, the procedure was termed oophoropexy and considered to be revolutionary, controversial and "cutting edge" fertility preservation. Ovarian function is compromised when damaged during surgery, exposed to radiation, and/or chemotherapy. Chemotherapy has been found to have a highly variable chance of acute ovarian failure. In general, for gynecological malignancies, cervical and uterine cancers are the most likely indications for adjuvant or definitive radiation treatment to the pelvis, but pelvic radiation is also done for Hodgkin's lymphoma, pediatric sarcomas and rectal cancer. Ovarian function is almost guaranteed to be entirely lost without some intervention before pelvic radiation therapy. Ovarian transposition is a relatively simple option that should be considered with all patients at risk for ovarian failure due to radiation.
  • Chapter 32 - Molecular and cellular integrity of cultured follicles
    pp 389-396
  • View abstract

    Summary

    Patients with early cervical cancer (FIGO stage IB1 or less) are conventionally considered treated with a surgical approach while those with more advanced disease are treated by radiotherapy with concurrent chemotherapy. Dargent's operation is the realization of a laparoscopic pelvic lymph-node dissection associated with a radical cervical amputation through a vaginal approach. Dargent's operation or radical trachelectomy enables preservation of fertility among women with early cervical cancer. The benefits of Dargent's operation are linked to the laparoscopic approach, which reduces the risk of adhesions on pelvis organs and the vaginal route that allows the preservation of uterine body and its optimal vascularization. Following the excellent results achieved by the Dargent's operation, several teams have proposed operating variants through laparotomy or laparoscopy. These modifications are subject to criticism because they are usually associated with the section of the uterine arteries and, thus, with a partial devascularization of the uterus.
  • Chapter 33 - In vitro growth systems for human oocytes
    pp 397-408
  • From primordial to maturation
  • View abstract

    Summary

    Ovarian cancers are classified as epithelial (including borderline and malignant tumors) and non-epithelial cancers. The standard treatment of borderline ovarian tumours (BOT) consisted of a total abdominal hysterectomy and bilateral salpingo-oophorectomy, peritoneal cytology, omentectomy and multiple peritoneal biopsies. The differential criterion between epithelial ovarian cancer (EOC) and BOT is the invasion of the ovarian stroma. The standard surgical procedure for EOC is a radical hysterectomy with bilateral salpingo-oophorectomy. Non-epithelial malignant tumors are characterized by: the occurrence of disease in younger patients; and a good prognosis of this tumor. Conservative treatment yields good fertility results and does not affect the survival of patients with BOT. It should be considered for young women desiring fertility, even if peritoneal implants are discovered at the time of initial surgery. In case of infertility, medically-assisted procreation techniques may be proposed to patients with stage I BOT with a limited number of stimulation cycles.
  • Chapter 34 - Contributions of ovarian stromal cells to follicle culture
    pp 409-420
  • View abstract

    Summary

    Survival rates after cancer have increased significantly in recent decades; however, these treatments also have drawbacks and patients (or parents in the case of children) must be informed of the long-term side effects of oncological treatments and the possible options for preserving the fertility of these patients. In oncological patients two special circumstances often arise: a short time to stimulate ovulation and the necessity of not reaching high estradiol levels. In applying embryo-freezing techniques to preserve the fertility of oncology patients, it is very important to know the couple's preference for the disposition of any unused embryos. Up to now, embryo cryopreservation has been the only clinically accepted method for preserving the fertility of oncology patients before they undergo chemotherapy and/or radiotherapy. The post-thawing pregnancy rates are acceptable and are around 30% per cryoreplacement depending on the number of embryos available and their quality.
  • Chapter 36 - Clinical potential of in vitro maturation
    pp 431-439
  • View abstract

    Summary

    Ovarian cryopreservation presents a valid alternative to egg freezing in some circumstances. The possibility to store oocytes for a later use is also an important consideration for women who choose to postpone motherhood for personal or professional reasons. Any newly developed protocol should consider the biochemical and physical properties of the oocyte. In addition to surviving the cryopreservation/warming process, the oocyte needs to maintain competence to fertilize and develop in vitro to the appropriate embryonic stage without any structural alterations. Slow cooling protocol is characterized by a slow decreasing temperature rate. Several mathematical models define an optimal curve applicable to oocytes since the freezing rate is vital to achieve sufficient and progressive dehydration, and thereby minimize the potential of intracellular ice formation. During fresh cycles only a few oocytes can be inseminated; therefore, cryopreservation is the only option to avoid wastage of surplus eggs and consequent repeated ovarian stimulation.
  • Chapter 37 - From pluripotent stem cells to germ cells
    pp 440-447
  • View abstract

    Summary

    This chapter considers the evolution of the practical application of cryopreservation technology to achieve consistently acceptable levels of cryosurvival of this highly cryosensitive gamete while retaining its inherent competency. The majority of oocyte freezing applied clinically has been based directly on traditional human embryo cryopreservation protocols. Such protocols utilize a "slow-freeze/rapid-thaw" approach necessitating use of a programmable freezer, and these protocols have produced to date the majority of the approximately 900 offspring worldwide. With regard to vitrification as a means to cryopreserve oocytes, increased speed of cooling, through the use of better designed carriers and protocols that lessen the concentration of cryoprotectant used while hastening exposure and procedure times, has put this technology on the map, and excellent embryo quality can be obtained from vitrified oocytes. To date vitrification as a cryopreservation method has had relatively little practical impact on human assisted reproduction.
  • Chapter 38 - Artificial ovary
    pp 448-458
  • View abstract

    Summary

    Detection of minimal residual disease in ovarian tissue was carried out by histology, real-time quantitative polymerase chain reaction (RT-qPCR) and long-term xenografting. To avoid transferring malignant cells together with grafted ovarian tissue, ovarian follicles may be isolated from the surrounding tissue and then either cultured for in vitro follicle maturation or transplanted directly into the recipient. Transplantation of frozen-thawed isolated primordial follicles has been successfully carried out in mice, yielding normal offspring. After isolation and recovery of human follicles, the developmental capacity and viability of these isolated human follicles are evaluated after transplantation. New matrices have been developed based on hydrogels, foams or natural polymers which could be suitable to nestle the isolated follicles and form a kind of artificial ovary before grafting to the patient. This would allow patients at risk of ovarian metastasis to benefit also from ovarian tissue cryopreservation and transplantation.
  • Chapter 39 - Predicting ovarian futures
    pp 459-466
  • The contribution of genetics
  • View abstract

    Summary

    This chapter provides insight into the fertility management of cancer survivors with compromised or absent ovarian function and without cryopreserved material. It begins with the evaluation of the cancer survivor for pregnancy. A flow-chart of cancer survivor screening is shown. Standard ovarian stimulation for assisted reproductive technology (ART) results in high levels of circulating estrogen, potentially 10 times the peak levels of spontaneous cycles. The mechanics of oocyte donation involves a number of steps: the recruitment of suitable donors, informed consent of donors and recipients, matching of donors to recipients, ovarian stimulation of the donor and the retrieval of her oocytes. Third-party reproduction is one of the most ethically complex aspects of reproductive health care. The chapter addresses, among other things, issues that occur when preservation of fertility has not been possible or has not been the best choice for a given individual.
  • Chapter 40 - Psychological issues of cancer survivors
    pp 467-478
  • View abstract

    Summary

    Fertility preservation is now recognized as the most essential quality of life issue in young cancer survivors. This chapter discusses three urgent and critical problems involved with ovarian tissue cryopreservation and transplantation (cryoin-jury, ischemic tissue damage, cancer cell transmission). The risk of cancer cell transmission is a serious safety issue related to ovarian autotransplantation in cancer patient. There are three strategies, at least in theory, to mature follicles in frozen stored ovarian tissue: autotransplantation; xenotransplantation; and in-vitro culture. Recently, significant progress has been made in immature follicle culture techniques. As an alternative to ovarian tissue transplantation, whole ovary transplantation has been explored. In theory, whole intact ovary transplantation with vascular anastomosis can restore the full function of the ovary. The main challenge of whole ovary transplantation for fertility preservation is the development of effective cryotechnology for the whole organ.

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